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HIV & Aging Clinical Recommendations
The incidence of type 2 diabetes mellitus is reported to be as much as four times higher in patients living with HIV compared to uninfected patients and increases with increasing age. The incidence of the metabolic syndrome is also higher. The increase in risk in ART-treated patients may be related to the use of certain antiretroviral drugs, such as thymidine analogues and older protease inhibitors (Llibre 2009; De Wit 2008), obesity (Samaras 2009), hepatitis C coinfection. The use of newer protease inhibitors, such as boosted darunavir or atazanavir, did not demonstrate clinically significant changes insulin sensitivity (Aberg 2012). There is recent concern surrounding the potential for increased weight gain with newer integrase inhibitors (Sax 2020) and tenofovir alefenamide (Venter 2020; Taramasso 2020), which in turn, may lead to an increased the risk of diabetes mellitus. However, a recent study (Ursenbach 2020) did not show a statistically significant association of the use of integrase inhibitors (raltegravir and dolutegravir) with new-onset diabetes.
Prevention of diabetes is similar to the approach in uninfected older patients, focusing on lifestyle changes such as weight loss, aerobic exercise and proper diet. Screening for glucose intolerance should be performed regularly, including before and after initiation of ART (Simone 2008; Thompson 2020). These screening tests include glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), or oral glucose tolerance test. There are potential challenges with each of these tests. There is accumulating data that HbA1c may underestimate glycemia in people with HIV (Monroe 2015), due to multiple factors, including higher mean corpuscular volume, nucleoside reverse transcriptase inhibitor use (abacavir), and lower CD4 counts (Slama 2014). Fasting plasma glucose may be more difficult to obtain if patients need to return to the laboratory on a different day or if fasting is difficult. While oral glucose tolerance testing can be used as a screening test, it is more time intensive and less acceptable to patients. According to the American Diabetes Association (ADA) guidelines, people with HIV should be screened for diabetes and prediabetes with a fasting glucose test before starting antiretroviral therapy, at the time of switching antiretroviral therapy, and 3-6 months after starting or switching antiretroviral therapy (American Diabetes Association 2021). If initial screening results are normal, fasting glucose should be checked annually. The American Diabetes Association confers a diagnosis of diabetes when 1) the fasting plasma glucose is equal to or greater than 126 mg/dL, 2) 2-hour plasma glucose is equal to or greater than 200 mg/dL during oral glucose tolerance test, or 3) glycated hemoglobin is equal to or greater than 6.5% (American Diabetes Association 2021).
Management of patients may include switching to less glucose intolerant antiretroviral drugs and following the American Diabetes Association guidelines (American Diabetes Association 2021). For younger patients and healthy older patients, the target glycated hemoglobin should be less than 7% (Chamberlain 2016; American Diabetes Association 2021) but should be increased to 8% for frail patients, especially if their life expectancy is less than 5 years, are at high risk for hypoglycemia, polypharmacy or drug interactions (Reuben 2015). Recent studies have shown no benefit and possible harm from tight glucose control in type 2 diabetes mellitus (Wilson 2011). Care of patients living with both HIV and diabetes should focus on prevention of complications (such as foot ulcers, retinopathy, hypertension and vascular disease) as much as with HIV-uninfected patients. Renal function and presence of proteinuria should also be carefully monitored as both diabetes and HIV increase the risk of renal disease. Luckily the incidence of end stage renal disease due to diabetes in people with HIV has declined (Abraham 2015). There is increasing prevalence of obesity in the older population and since obesity is a risk factor for development of the metabolic syndrome and hyperglycemia, clinicians should counsel their older patients with HIV to maintain proper weight and body mass index (BMI). In one cohort study, the increase in body mass following the initiation of ART was associated with an increased risk of diabetes (Achhra 2016).
Morphologic changes are common in older patients living with HIV/AIDS. Increasing age is risk factor for loss of subcutaneous fat (lipoatrophy) and/or increase in central fat deposition (lipohypertrophy) but newer ART regimens are less likely to promote these changes. Older patients should be switched from thymidine analogues to INSTI’s which are less likely to cause direct metabolic pertubations that may lead to morphologic changes. Treatment options for patients with lipohypertrophy can include surgical removal of fat or use of growth hormone releasing factor.
Treatment of Diabetes Mellitus
Lifestyle modification (diet and exercise) should be the first step in managing patients with diabetes. Pharmacologic treatment of diabetes for patients living with HIV follows the same guidelines as for those patients without HIV. Metformin, which will result in a 1% decline in glycosylated hemoglobin, should be the first-line medication, unless there is a contraindication such as significant renal insufficiency (eGFR <30 ml/min). Sulfonylureas, thiazolidinediones, or insulin can be used as second agents if necessary. However, the use of newer classes, such as GLP-1 receptor agonists and SGLT2 inhibitors, in people with HIV is becoming more common due to the weight loss effects of these medications, which may also help blood pressure and visceral adiposity. Saxagliptin, a DPP-4 inhibitor, should be used with caution with CYP3A inhibitors (Monroe 2015).
Assessment and Treatment of Complications of Diabetes
The approach to screening for and managing the complications of diabetes in patients living with HIV are similar to those in uninfected patients. Screening for hypertension, renal disease, hyperlipidemia, microvascular complications (retinopathy, neuropathy and nephropathy) need to be done on a regular basis. The JNC 8 guidelines recommend treating systolic pressures above 140 and diastolic pressures above 90 (Sangarlangkarn 2016a). BP targets for frail elderly can be higher due to the increased risk of orthostatic hypotension. Unless contraindicated, aspirin therapy should be initiated. For the treatment of hyperlipidemia, pitavastatin is the only oral lipid lowering agent that does not interact with ART (Monroe 2015). Lower dose atorvastatin may also be used. Pregabalin and duloxetine are recommended as initial treatment for painful peripheral neuropathy. Gabapentin may be considered but it does have an approved indication for this (Pop-Busui 2017).
Samaras K. Prevalence and pathogenesis of diabetes mellitus in HIV-1 infection treated with combined antiretroviral therapy. J Acquir Immune Defic Syndr 2009; 50(5): 499-505.
Aberg JA, Tebas P, Overton ET, Gupta SK, Sax PE, Landay A, et al. Metabolic effects of darunavir/ritonavir versus ataznavir/ritonavir in treatment-naïve, HIV type 1-infected subjects over 48 weeks. AIDS Res Hum Retroviruses 2012; 28(10):1184-95.
Sax PE, Erlandson KM, Lake JE, Mccomsey GA, Orkin C, Esser S, et al. Weight gain following initiation of antiretroviral therapy: risk factors in randomized comparative clinical trials. Clin Infect Dis 2020; 71(6):1379-89.
Venter WDF, Moorhouse M, Sokhela S, Fairlie L, Mashabane N, Masenya M, et al. Dolutegravir plus two different prodrugs of tenofovir to treat HIV. N Engl J Med 2019; 381(9): 803-15.
Taramasso L, Berruti M, Briano F, di Biagio A. The switch from TDF to TAF determines weight gain in patients on rilpivirine-based regimen. AIDS 2020; 34(6):877-81.
Ursenbach A, Max V, Maurel M, Bani-Sadr F, Gagneux-Brunon A, Garraffo R, et al. Incidence of diabetes in HIV-infected patients treated with first-line integrase strand transfer inhibitors: a French multicenter retrospective study. J Antimicrob Chemother 2020; 75(11):3344-8.
Thompson MA, Horberg MA, Aguw AL, Colasanti JA, Jain MK, Short WR, et al. Primary care guidance for persons with human immunodeficiency virus 2020 update by the HIV Medicine Association of the Infectious Diseases Society of America Clin Infect Dis 2020.
Slama L, Palella FJ, Abraham AG, Li X, Vigouroux C, Pialoux G, et al. Inaccuracy of haemoglobin A1c among HIV-infected men: effects of CD4 cell count, antiretroviral therapies and haematological parameters. J Antimicrob Chemother 2014; 69(12): 3360-7.
American Diabetes Association. 2. Classification and diagnosis of diabetes: Standards of medical care in diabetes – 2021. Diabetes Care 2021; 44(Suppl. 1): S15-33.
American Diabetes Association. 6. Glycemic targets: Standards of medical care in diabetes – 2021. Diabetes Care 2021: 44(Suppl. 1): S73-S84.
Reuben DB, Herr KA, Pacala JT, Potter JF, American Geriatrics S. Geriatrics at your fingertips. New York. eBook: American Geriatrics Society; 2016.
Purpose of this Program: The AAHIVM, ACRIA and AGS (collectively, the “Sponsors,” “we” or “us”) are sponsors of this Website and through it seek to address the unique needs and challenges that older adults of diverse populations living with HIV face as they age. However, the information in this Website is not meant to supplant the advice provided in a doctor-patient relationship.
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